Method and multicomponent conjugates for treating cancer

Abstract

The present invention provides a method for treating cancer in a mammal and to using multicomponent conjugates of formula: A--B--C, where “B” may be present or absent, “A” comprises at least one specific anti-tumor binding protein recognizing a tumor associated receptor, “B” comprises at least one molecule to which “A” and “C” bind, “C” comprises at least one specific anti-platelet binding protein recognizing a receptor present on the outer surface of a blood platelet. The multicomponent conjugates provide the exquisite binding specificity, which enables attaching the blood platelets either to the outer surface of the cancer cells, or to the outer surface of a component of the tumor associated vasculature or stroma, and thus, stimulating the formation of blood clots within the blood vessels around and in-between cancer cells, leading to their destruction.

1 . A multicomponent conjugate comprising a formula A--B--C, wherein “A” comprises at least one specific anti-tumor binding protein recognizing a tumor associated antigen or receptor, “B” comprises at least one molecule to which “A” and “C” bind, and “C” comprises at least one specific anti-platelet binding protein recognizing a receptor or an antigen present on the outer surface of a blood platelet.  
     
     
         2 . The multicomponent conjugate of  claim 1 , wherein “A” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a cancer cell.  
     
     
         3 . The multicomponent conjugate of  claim 1 , wherein “A” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a component of a tumor associated vasculature or stroma.  
     
     
         4 . The multicomponent conjugate of  claim 1 , wherein “B” comprises a streptavidin or avidin molecule, and from 2 to 4 biotin molecules.  
     
     
         5 . The multicomponent conjugate of  claim 1 , wherein “C” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a blood platelet.  
     
     
         6 . A multicomponent conjugate comprising a formula A--C, wherein “A” comprises at least one specific anti-tumor binding protein recognizing a tumor associated antigen or receptor, and “C” comprises at least one specific anti-platelet binding protein recognizing a receptor or an antigen present on the outer surface of a blood platelet.  
     
     
         7 . The multicomponent conjugate of  claim 6 , wherein “A” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a cancer cell.  
     
     
         8 . The multicomponent conjugate of  claim 6 , wherein “A” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a component of a tumor associated vasculature or stroma.  
     
     
         9 . The multicomponent conjugate of  claim 6 , wherein “C” is an antibody or a binding fragment of an antibody recognizing an antigen present on the outer surface of a blood platelet.  
     
     
         10 . In a mammal, a method for destroying tumor cells, comprising administering to said mammal a number of multicomponent conjugates, each having the formula A--C, wherein “A” comprises at least one specific anti-tumor binding protein recognizing a tumor associated antigen or receptor, and “C” comprises at least one specific anti-platelet binding protein recognizing a receptor or an antigen present on the outer surface of a blood platelet.  
     
     
         11 . The method of  claim 10 , wherein the said mammal is a human.  
     
     
         12 . In a mammal, a method for destroying tumor cells, comprising administering to said mammal a number of multicomponent conjugates, each having the formula A--B--C, wherein “A” comprises at least one specific anti-tumor binding protein recognizing a tumor associated antigen or receptor, “B” comprises at least one molecule to which “A” and “C” bind, and “C” comprises at least one specific anti-platelet binding protein recognizing a receptor or an antigen present on the outer surface of a blood platelet.  
     
     
         13 . The method of  claim 12 , wherein the multicomponent conjugates are prepared in vitro and administered to the said mammal by intravenous injection.  
     
     
         14 . The method of  claim 12 , wherein “A” is an anti-tumor antibody recognizing a tumor associated antigen, “B” comprises an avidin, or an avidin like molecule and  2  biotin molecules, and “C” is an anti-platelet antibody recognizing an antigen present on the outer surface of a blood platelet, with the multicomponent conjugates being assembled in vivo within the body of the said mammal.  
     
     
         15 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of multicomponent conjugates, each including at least one specific anti-tumor binding protein recognizing a tumor associated antigen or receptor, and at least one specific anti-platelet binding protein recognizing a receptor or an antigen present on the outer surface of a blood platelet;    b) intravenous injection of a number of biotinylated anti-platelet antibodies; and    c) intravenous injection of a number of avidin, or avidin like molecules.    
     
     
         16 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of biotinylated anti-tumor antibodies; and    b) intravenous injection of a number of biotinylated anti-platelet antibodies-avidin or avidin like complexes.    
     
     
         17 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of biotinylated anti-tumor antibodies-avidin or avidin like complexes;    b) intravenous injection of a number of biotinylated anti-platelet antibodies; and    c) intravenous injection of a number of avidin or avidin like molecule.    
     
     
         18 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of biotinylated anti-tumor antibodies and a number of biotinylated anti-platelet antibodies; and    b) intravenous injection of a number of avidin or avidin like molecules.    
     
     
         19 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) Intravenous injection of a number of biotinylated anti-tumor antibodies; and    b) Intravenous injection of a number of, in vitro prepared, blood platelets having biotinylated anti-platelet antibodies-avidin or avidin like complexes attached to their outer surfaces.    
     
     
         20 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugates within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of biotinylated anti-tumor antibodies-avidin or avidin like complexes;    b) intravenous injection of a number of, in vitro prepared, blood platelets having biotinylated anti-platelet antibodies attached to their outer surfaces; and    c) intravenous injection of a number of avidin or avidin like molecules.    
     
     
         21 . The method of  claim 14 , wherein the said in vivo assembling of the multicomponent conjugate within the body of the mammal comprises the steps of: 
 a) intravenous injection of a number of biotinylated anti-tumor antibodies;    b) intravenous injection of a number of avidin or avidin like molecules;    c) intravenous injection of a number of, in vitro prepared, blood platelets having biotinylated anti-platelet antibodies attached to their outer surfaces; and    d) intravenous injection of a number of avidin or avidin like molecules.    
     
     
         22 . The method of  claim 14 , wherein the said mammal is a human.